Methods for heating microscope slides carrying specimens

ABSTRACT

A slide processing apparatus controls the temperature and orientation of a microscope slide carrying one or more specimens. The apparatus heats the specimen-bearing microscope slide while the slide is oriented to both facilitate adhesion between the specimens and the slide and control movement of the specimens relative to the microscope slide. A slide dryer of the apparatus conductively heats the specimens using a conductive slide heater that physically engages the microscope slide.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/102,598, filed Aug. 13, 2018 (U.S. Pat. No. 10,520,403), which is acontinuation of U.S. application Ser. No. 16/010,357, filed Jun. 15,2018 (U.S. Pat. No. 10,429,280), which is a continuation of U.S.application Ser. No. 13/128,856, filed on May 11, 2011 (U.S. Pat. No.10,184,862), which is a National Phase Application of PCT ApplicationNo. PCT/US2009/064235, filed Nov. 12, 2009, which claims priority toU.S. Provisional Patent Application No. 61/113,964, filed on Nov. 12,2008 which are all hereby incorporated by reference in their entireties.

TECHNICAL FIELD

The present invention relates generally to methods and apparatuses forprocessing slides carrying specimens. More specifically, the inventionis related to adhering specimens onto microscope slides.

BACKGROUND

Tissue analysis is a diagnostic tool used by physicians, such aspathologists, to diagnose different types of illnesses and by medicalresearchers to obtain information about pathology, tissue composition,and tissue architecture. A wide range of different procedures arecommonly used to prepare a tissue sample for tissue analysis. Many typesof tissue are relatively soft and pliable and, thus, not suitable forsectioning. Techniques for preparing tissue samples include fixing thetissue, embedding the tissue in a material, sectioning the embeddedtissue, and transferring the tissue sections onto microscope slides forsubsequent processing and analyses, such as staining,immunohistochemistry, or in-situ hybridization. To section a tissuesample for optical microscope examination, a relatively thin strip oftissue can be cut from a large tissue sample so that light may betransmitted through the thin strip of tissue. An average thickness ofthe strip of tissue is often on the order of about 2 microns to about 8microns.

Water is often used to facilitate transfer of the thin strips of tissueonto microscope slides. A residual droplet of water trapped between themicroscope slide and the thin strips of tissue will cause the thinstrips of tissue to float on the slide. The floating tissue sections ofthese wet slides are susceptible to movement along the front surface ofthe microscope slides. If the tissue samples move too far, the samplesmay fall off of the microscope slide. If the physician is unaware of thesample falling off of the microscope slide, a diagnosis may be madebased on an incomplete test result, which may ultimately contribute to amisdiagnosis. For example, if a set of tissue samples are floating onresidual water on a slide, one of the tissue samples may fall off theslide during a drying process. The tissue sample that fell off may be atissue sample needed for a proper diagnosis.

Horizontal hotplates and convection ovens are often used to heat and drywet microscope slides. If a horizontal hotplate is used, it may take arelatively long period of time to evaporate the water beneath the tissuesample on a horizontally oriented slide. Additionally, the contact anglebetween the water and the slide often increases when embedding materialof the sample melts and reaches the front surface of the slide. If themicroscope slide moves or is not level during this drying process, thetissue sample may move a significant distance relative to the slide and,in some circumstances, may fall off of the microscope slide. If spacedapart tissue samples (e.g., a row of evenly spaced tissue samples) movesignificant distances relative to one another during the drying process,a physician may become concerned that one or more of the tissue samplesfell off of the microscope slide. The physician may discard thatsample-bearing slide and prepare a completely new sample-bearing slideto ensure that a complete set of tissue samples is analyzed. It may benecessary to obtain additional tissue samples from the subject.Convection ovens take a relatively long time to dry slides. Conventionalconvection ovens can dry vertically oriented slides in about 30 minutesto about 2 hours.

SUMMARY

At least some embodiments disclosed herein include an apparatusconfigured to dry a specimen on a microscope slide. The apparatuscontrols the temperature of a microscope slide carrying the specimen.The apparatus heats the specimen while the microscope slide is held in aposition that both facilitates adhesion between the specimen and theslide and controls movement of the specimen, if any, relative to themicroscope slide.

The apparatus, in some embodiments, holds the microscope slide in a nearvertical orientation to limit, minimize, or substantially preventmovement of the specimen relative to the microscope slide. The specimencan remain at the same general position relative to the microscope slidebefore and/or during a drying process. In certain embodiments, thespecimen is adhered to an area of the slide over which the specimen wasoriginally placed. Additionally, residual transfer fluid between thespecimen and the slide drains so as to bring the specimen into physicalcontact with the slide, thereby reducing drying time. The specimen canbe heated to couple a back surface of the specimen to a front surface ofthe slide.

In some embodiments, a dryer is adapted to hold a carrier in an uprightposition to allow residual transfer fluid between a specimen and thecarrier to move away from an interface between the specimen and thecarrier. A conductive heater of the dryer is capable of generating asufficient amount of heat for conductively heating at least a portion ofthe specimen to a melt point. The specimen includes a biological sampleof tissue and another material, such as an embedding material with arelatively low melt point. The melted embedding material can be cooledto fixedly couple the specimen to the carrier. In certain embodiments,the carrier is a slide, such as a microscope slide.

The conductive heater supports and delivers heat to a back surface ofthe carrier such that heat is conducted across the thickness of thecarrier to the specimen on a front surface of the carrier. At least aportion of the embedding material is melted. The melted portion of theembedding material allows the specimen to physically contact the frontsurface of the carrier. When cooled, the specimen is securely attachedto the front surface of the carrier.

In some embodiments, an apparatus for processing a microscope slidecarrying a specimen includes a slide dryer. The specimen can include abiological sample and an embedding material. The slide dryer can dry thespecimen and embedding material without unwanted migration of thebiological sample. In some embodiments, the slide dryer is configured tohold a microscope slide in a substantially vertical orientation. Theslide dryer includes a controller and a conductive slide heatercommunicatively coupled to the controller. The conductive slide heateris adapted to generate a sufficient amount of heat in response to asignal from the controller so as to conductively heat the specimen onthe microscope slide to a melt point of the embedding material. Theslide dryer can efficiently dry the microscope slide even if thesurrounding ambient temperature is relatively low, for example, at roomtemperature.

In some embodiments, a slide dryer is configured to hold the microscopeslide in a vertical orientation while the wet mount microscope slide isdried. A conductive slide heater selectively heats the microscope slideand biological sample carried thereon to adhere the biological sample tothe microscope slide.

In other embodiments, a slide dryer includes a conductive slide heaterthat has an engagement face and an angle of inclination of about atleast 75 degrees. The conductive slide heater is adapted to heat theengagement face to a temperature equal to or greater than about 50degrees Celsius.

In some embodiments, an apparatus for processing a microscope slideincludes a drying station, a processing station, and a transport device.In some embodiments, the drying station includes a slide dryerconfigured to hold a microscope slide in a substantially verticalorientation and to generate heat for conductively heating at least onespecimen carried by the microscope slide for a period, such as a dryingperiod. The processing station is adapted to process the specimen on themicroscope slide after the drying period. The transport device isconfigured to transport microscope slides between the slide dryer andthe processing station.

In some embodiments, a method for processing a specimen on a microscopeslide is provided. The method includes positioning the specimen on amicroscope slide such that residual transfer fluid is between thespecimen and the microscope slide. The microscope slide is held in asubstantially vertical orientation to urge the residual transfer fluidfrom between the specimen and the microscope slide. The microscope slideis conductively heated while the microscope slide is in thesubstantially vertical orientation using a conductive slide heater thatphysically engages the microscope slide.

In other embodiments, a method for processing a specimen carried by amicroscope slide includes positioning a microscope slide carrying aspecimen in a substantially vertical orientation. The specimen floats onresidual transfer fluid trapped on the microscope slide. The residualtransfer fluid is drained from between at least a portion of thefloating specimen and the microscope slide. The microscope slide isconductively heated using a conductive slide heater.

A slide dryer, in some embodiments, can dry a microscope slide generallyindependent of a temperature of the ambient air. Heat can beconductively delivered to the microscope slide to rapidly heat themicroscope slide generally independent of the surrounding airtemperature. A user can easily access the slide dryer to manually loadmicroscope slides onto the slide dryer and to remove the microscopeslides after a drying period. In some embodiments, the slide dryer canhave a controller that can be programmed to perform different types ofdrying processes.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting and non-exhaustive embodiments are described with referenceto the following drawings. The same reference numerals refer to likeparts or acts throughout the various views, unless otherwise specified.

FIG. 1 is a pictorial view of a slide dryer for heating microscopeslides, in accordance with one embodiment.

FIG. 2 is a side elevational view of the slide dryer of FIG. 1 holding aplurality of specimen-carrying microscope slides.

FIG. 3 is a front elevational view of the slide dryer andspecimen-carrying microscope slides of FIG. 2.

FIG. 4 is a partial cross-sectional view of components of a slide dryerand a specimen-carrying microscope slide.

FIG. 5 is a flow chart of one method of processing a biological sample.

FIG. 6 is an elevational view of a specimen and residual transfer fluidpositioned on a microscope slide supported by a conductive slide heater.

FIG. 7 is an elevational view of a specimen-carrying microscope slidebefore a back surface of a specimen is adhered to a front face of theslide.

FIG. 8 is an elevational view of the specimen of FIG. 7 adhered to themicroscope slide.

FIG. 9 is a pictorial view of a slide dryer with a cover and aconductive slide heater capable of holding a plurality of microscopeslides that are spaced apart from one another.

FIG. 10 is a pictorial view of a conductive slide heater for holding tworows of microscope slides.

FIG. 11 is a pictorial view of an apparatus for processing microscopeslides, in accordance with one illustrated embodiment.

FIG. 12 is a side elevational view of the apparatus of FIG. 11.

FIG. 13 is a cross-sectional view of the apparatus of FIG. 11 takenalong a line 13-13 of FIG. 12.

DETAILED DESCRIPTION

FIG. 1 shows a slide dryer 100 capable of drying one or morespecimen-carrying microscope slides. The slide dryer 100 can heat themicroscope slides and specimens carried thereon in order to dry theslides and/or specimens, to couple the specimens to the slides, and/orto perform any other desired thermal processing. The specimen-carryingmicroscope slides are held in an orientation that promotes removal ofresidual transfer fluid between the specimens and the respectivemicroscope slides while limiting, minimizing, or substantiallyeliminating unwanted movement of the specimens. The specimen-carryingslides are dried to fixedly couple the specimens to the respectiveslides. After the specimens are fixedly coupled to the slides, thespecimen-carrying slides are removed from the slide dryer 100 forsubsequent processing and tissue analyses, such as staining,immunohistochemistry, in-situ hybridization, or other processing. Theillustrated slide drying 100 is portable and can be readily carried(e.g., manually transported) by a person. In a laboratory setting, theslide dryer 100 can be manually transported between workstations.

The microscope slides can be held in substantially vertical orientationsto promote removal of residual transfer fluid trapped beneath thespecimens to reduce drying times. A region of a slide beneath a specimencan be rapidly dried by draining flowable residual transfer fluid awayfrom the specimen. As such, only a portion of the residual transferfluid is evaporated to dry the region of the slide facing the specimen.The slide dryer 100 produces heat to both dry the slides and facilitatecoupling of the specimens to the slides. The specimens can include,without limitation, a biological sample (e.g., a tissue sample) and amaterial (e.g., an embedding material) in which the sample is embedded.

At least a portion of the embedding material is melted, brought intocontact with the slide, and solidified so as to attach the biologicalsample directly to the slide. The embedding material can move towardsthe microscope slide and can be ultimately deposited on the slide. Ifthat material is more hydrophobic than the material of the slide and theresidual transfer fluid (e.g., water), the embedding material maypromote beading of the fluid. As the embedding material coats the slide,a contact angle between the fluid and slide will increase. Because themicroscope slide is in the upright orientation, the residual transferfluid will tend to accumulate at a lower end of the specimen due togravity. An upper end of the specimen can physically contact the frontface of the slide and minimize, limit, or substantially prevent unwantedmigration of the specimen. After a sufficient amount of residualtransfer fluid has accumulated, it can drain downwardly away from thespecimen, thereby leaving the specimen on the front face of the slide.This process can be performed on a wide range of wetted microscopeslides.

The illustrated slide dryer 100 of FIG. 1 includes a conductive slideheater 110, a controller 114, and a main body 118 that houses internalcomponents of the slide dryer 100. The conductive slide heater 110 canphysically contact and support one or more microscope slides. The mainbody 118 includes a slide support 120 adjacent to the conductive slideheater 110.

The conductive slide heater 110 and slide support 120 can cooperate tohold a microscope slide in a substantially vertical orientation suchthat heat generated by the conductive slide heater 110 is transferred tothe microscope slide for a desired period, such as a drying period. Theconductive slide heater 110 is capable of generating a sufficient amountof heat in response to a signal from the controller 114 so as toconductively heat the specimen to a desired temperature. Residualtransfer fluid can flow away from the specimen, evaporate, and/orotherwise be removed from the specimen-carrying microscope slide. Theheated specimen is brought into physical contact with the microscopeslide. The specimen can be elevated to a temperature that facilitatesadhesion between the specimen and the microscope slide, as discussed inconnection with FIGS. 6-9.

FIGS. 2 and 3 show a plurality of microscope slides 130 a, 130 b, 130 c(collectively 130) resting against the conductive slide heater 110 andon an upper surface 136 of the slide support 120. The microscope slides130 can be generally flat transparent substrates carrying specimens 132for examination using equipment, such as optical equipment (e.g., amicroscopic). For example, each microscope slide 130 may be a generallyrectangular piece of a transparent material (e.g., glass) having a frontface for receiving specimens and a back face for engaging the slidedryer 100. The microscope slides 130 may be charged or unchargeddepending on the application and can have a wide range of differentdimensions. In some embodiments, the slides 130 have a length of about 3inches (75 mm) and a width of about 1 inch (25 mm) and, in certainembodiments, may include a label, such as a barcode. In someembodiments, the slides have a length of about 75 mm, a width of about25 mm, and a thickness of about 1 mm. The microscope slides 130 can bein the form of standard microscope slides. The illustrated microscopeslides 130 carry the uncovered specimens 132 (e.g., without coverslips).In some embodiments, the dimensions of slide support 120 are such that alabel on a slide 130 is located on a face of the slide opposite theslide support and above the portion of the slide that is in contact withthe slide support. In this manner, the label can be protected from heatduring the drying process.

The main body 118 rests on a generally horizontal support surface 140such that the microscope slides 130 are held generally upright. Thecontroller 114 may be conveniently accessed by a user to controloperation of the slide dryer 100. FIGS. 1-3 show the controller 114communicatively coupled to the conductive slide heater 110 including ahousing 146, a display 150, and an input device 154. The display 150 canbe a screen or other display device. The input device 154 can include,without limitation, one or more buttons, keyboards, input pads, buttons,control modules, or other suitable input elements. The illustrated inputdevice 154 is in the form of an input pad, such as a touch pad, used toprogram the slide dryer 100.

The controller 114 can generally include, without limitation, one ormore central processing units, processing devices, microprocessors,digital signal processors, central processing units, processing devices,microprocessors, digital signal processors (DSP), application-specificintegrated circuits (ASIC), readers, and the like. To store information(e.g., a drying program), the controller 114 can also include, withoutlimitation, one or more storage elements, such as volatile memory,non-volatile memory, read-only memory (ROM), random access memory (RAM),and the like. The controller 114 can be programmed based on the desiredprocessing of the specimen-carrying slides. In a fixed temperature modeof operation, the controller 114 is used to maintain the conductiveslide heater 110 at a generally constant temperature. In a variabletemperature mode of operation, the controller 114 is used to adjust thetemperature of the conductive slide heater 110. The controller 114 canstore one or more programs for controlling the operation of theconductive slide heater 110. The input device 154 can be used to switchbetween different programs, modes of operation, or the like.

Referring to FIGS. 1-3, heat can be efficiently transferred across thethicknesses of the microscope slides 130. The illustrated conductiveslide heater 110 of FIG. 2 has a height H that is greater than or equalto the lengths of specimen mounting regions of the slides 130. Asubstantial portion of a longitudinal length L_(s) of each microscopeslide 130 can contact the conductive slide heater 110 to facilitategenerally even heat distribution throughout the entire mounting regions.In some embodiments, the height H is at least about 2.5 inches (63.5mm), about 2.75 inches (70 mm), or about 2.9 inches (74.7 mm), as wellas ranges encompassing such heights. Upper ends 139 a, 139 b, 139 c ofthe slides 130 a, 130 b, 130 c, respectively, can protrude upwardly pastthe slide dryer 100 for conveniently grasping the slides 130.

A longitudinal length L of the conductive slide heater 110 can beselected based on the desired number of microscope slides 130 to beprocessed. The length L can be increased or decreased to increase ordecrease the number of microscope slides that can be processed, spacingbetween the microscope slides, or the like. The illustrated embodimentof FIG. 3 has three spaced apart microscope slides 130. In someembodiments, the length L is at least 6 inches (152 mm) to allow atleast three microscope slides 130 to be concurrently processed. Otherdimensions are also possible.

The conductive slide heater 110 can be a plate having a generallyrectangular shape, as viewed from the side (see FIG. 3). The thermalproperties of the conductive slide heater 110 may be selected based ondesired processing criteria, such as the desired processing temperature,temperature distribution, rates of heating/cooling, and the like. Forexample, an engagement face 160 of the slide heater 110 can have arelatively low thermal mass and a high thermal conductivity for rapidlytransferring heat across the entire face 160. The engagement face 160can have a substantially uniform heat distribution to ensure that all ormost of the slides 130 are maintained at substantially the sametemperature.

The conductive slide heater 110 can be made, in whole or in part, of oneor more thermally conductive materials, for example, metals such ascopper, steel, aluminum, iron, combinations thereof, or the like. Insome embodiments, the engagement face 160 is made mostly of steel (e.g.,stainless steel) and is highly resistant to wear and corrosion. In otherembodiments, the engagement face 160 is made mostly of copper forrapidly transferring heat between internal heating elements and theslides 130. Advantageously, the number of internal heating elements,such as resistive heaters of the heater 110, can be reduced because ofthis rapid heat transfer. The conductive slide heater 110 can have amulti-layer construction to enhance wear characteristics and thermalperformance. For example, the engagement face 160 can be a thin sheet ofsteel, and an inner layer of copper in the heater 110 can helpdistribute and deliver heat to the face 160. In other embodiments, theconductive slide heater 110 has a monolayer construction.

The engagement face 160 can be substantially flat to increase the areasof contact between the slides 130 and the face 160. The engagement face160 can be a highly polished face that is extremely flat for contactingmost or substantially all of overlying portions of the slides 130. Insome embodiments, the engagement face 160 is configured to minimize,limit, or substantially prevent relative movement of the microscopeslides 130. For example, anti-migration features (e.g., protrusions,protuberances, grooves, partitions, texturing, and the like) can beincorporated into the face 160.

The main body 118 of FIGS. 1-3 has a base 170 for resting on the surface140. The main body 118 protects internal components, even when the slidedryer 100 is used in harsh environments, including, without limitation,corrosive environments often found in labs, or other testing sites. Theslide support 120 is integrally formed with the main body 118. In theillustrated embodiment, the upper surface 136 extends generallyperpendicularly with respect to the engagement face 160. When the lowerends of the microscope slides 130 rest upon the upper surface 136, theback surfaces 141 of the slides 130 (see FIG. 2) lie flat against theengagement face 160.

FIG. 4 shows the controller 114, a power source 200, a line 202 thatdelivers electrical power to the conductive slide heater 110, and asensor 212 for evaluating operation of the slide heater 110. A line 220communicatively couples the controller 114 to the sensor 212. Theillustrated conductive slide heater 110 includes an outer portion 210and a thermo-electric element 204. The term “thermo-electric element” isa broad term that includes, without limitation, one or more electricdevices capable of generating heat and/or absorbing heat.

Substantially all or most of the engagement face 160 can have asubstantially uniform temperature when the element 204 is activated. Forexample, substantially all or most of the engagement face 160 can bewithin a temperature range of about 10 degrees Celsius. In certainembodiments, the engagement face 160 is maintained at generally the sametemperature. For example, the average temperature of the engagement face160 can be in a range of about 5 degrees Celsius. In other embodiments,different portions of the engagement face 160 can be maintained atdifferent temperatures to accommodate drying of slides holding differenttypes of tissues and for tissues embedded with different embeddingmaterials.

In some embodiments, including the illustrated embodiment of FIG. 4, theouter portion 210 is a hollow plate, and the thermo-electric element 204is a heating element adapted to convert electrical energy to thermalenergy. When the heating element 204 generates heat, heat is transferredthrough the portion 210 and is absorbed by the microscope slide 130.Heat is ultimately transferred from the slide 130 to the specimens 132.The amount of electrical energy delivered to the element 204 can beincreased or decreased to increase or decrease the temperature of thespecimens 132.

The heating element 204 can be a resistive heating element. A wide rangeof different types of resistive heating elements (e.g., plate resistiveheaters, coil resistive heaters, strip heaters, or the like) can beselected based on the desired operating parameters. Other types ofthermal elements, such as cooling elements, heating/cooling elements, orthe like, can be utilized. As used herein, the term “cooling element” isa broad term that includes, without limitation, one or more elementscapable of actively absorbing heat so as to effectively cool at least aportion of the conductive slide heater 110. For example, a coolingelement can be a cooling tube or channel through which a chilled fluidflows. In some embodiments, the conductive slide heater 110 includesheating elements for producing heat during a heating period and coolingelements for absorbing heat during a cooling period.

In some embodiments, the element 204 is a heating/cooling element, suchas a Peltier device. Peltier devices may be solid state components whichbecome hot on one side and cool on an opposing side, depending on adirection of current passed therethrough. By simply selecting thedirection of current, the Peltier device 204 can be employed to heat theengagement face 160 for a desired length of time. By switching thedirection of the current, the device 204 cools the engagement face 160.In other embodiments, the heating/cooling element 204 can be in the formof channels through which a working fluid flows. Heated fluid can bepassed through the channels for a heating period, and a chilled fluidcan be passed through the channels for a cooling period. The position,number, and type of heating/cooling elements 204 can be selected basedon the desired temperature profile of the conductive slide heater 210.

The thermal properties of the portion 210 can be selected to achieve adesired temperature distribution along a wall 211 of the engagement face160. For example, the portion 210 can be made, in whole or in part, of ahighly conductive material, such as copper, or other suitable materialwith sufficient thermal conductivity to reduce or limit any significantlocal temperature non-uniformities associated with discrete heatingelements 204. Because heat is lost to the surrounding air (e.g., air atroom temperature), the elements 204 can continually produce a constantflux. The interior portions of the slide heater 110 may be hotter thanthe periphery of the heater 110 because heat is dissipated faster fromthe periphery of the slide heater 110 due to its exposed edges. In someembodiments, an array of closely spaced heating elements 204 is used tomaintain a generally uniform temperature across the surface 160. Otherconfigurations are also possible.

The sensor 212 is a temperature sensor that detects the temperature ofthe heater 110 and sends one or more signals indicative of thattemperature. The sensor 212 can be mounted on a back surface 217 of theconductive slide heater 110, embedded in the heater 110, mounted on orembedded in the engagement face 160, or positioned at any other suitablelocation for measuring the temperatures of any portion of the slideheater 110 and/or the microscope slides 130. The sensor 212 can include,without limitation, one or more thermal couples, thermometers (e.g., anIR thermometer) pyrometers, resistance temperature detectors (RTDs),thermistors, or the like.

FIG. 5 is a flow diagram of one method of preparing and analyzing aspecimen. Generally, a specimen can be placed on a microscope slideusing a thin tissue section transfer fluid such as water. Thespecimen-carrying microscope slide is loaded into the slide dryer anddried such that the specimen is adhered to the microscope slide. Theslide dryer 100 rapidly dries the slide while minimizing, limiting, orsubstantially eliminating unwanted migration of the specimen relative tothe microscope slide. The specimen can remain at the same generalposition relative to the slide during the drying process. If a pluralityof specimens is mounted on the slide, the spacing between the specimenscan be maintained throughout the drying process. This may reduce oreliminate a physician's concern about tissue specimens falling off ofthe microscope slide. The specimen-carrying slide can then beconveniently transported and analyzed using a wide range of differentexamination techniques and equipment. This process is discussed indetail below.

A biological sample, such as a sample of tissue, is processed topreserve its characteristics, such as the tissue structure, the cellstructure, and the like. The tissue can be any collection of cellsmountable on a microscope slide including, without limitation, a sectionof an organ, tumor section, bodily fluid, smear, frozen section,cytology prep, or cell lines. For example, the tissue sample can be asample obtained using an incisional biopsy, a core biopsy, an excisionalbiopsy, a needle aspiration biopsy, a core needle biopsy, a stereotacticbiopsy, an open biopsy, a surgical biopsy, or the like.

At 250, a fixative is used to fix and preserve the sample. Fixatives canfix and preserve cellular structure, inhibit or substantially stopenzymatic action that may result in the purification or autolysis of thetissue, or the like. The fixation process can increase the rigidity ofthe tissue, thereby making it more convenient to section, as detailedbelow. Formaldehyde, ethanol, acetone, paraformaldehyde, or other typesof fixatives can be used. The type and number of fixatives can beselected based on the desired processes to be performed, such asstaining, cytological staining, immunohistochemistry, or in-situhybridization. After fixing the tissue sample, the tissue sample can bestored for a desired length of time.

At 260, the sample is embedded in a material that has mechanicalproperties that may facilitate sectioning. Materials for embeddinginclude, but are not limited to, paraffin, resin (e.g., plastic resins),polymers, agarose, nitrocellulose, gelatin, mixtures thereof, or thelike. In some embodiments, the embedding material comprises mostly orentirely of paraffin. Paraffin is a white or generally colorless waterinsoluble solid substance that is resistant to many reagents. Forexample, paraffin can be a mixture of hydrocarbons chiefly of thealkaline series obtained from petroleum. A wide range of differentmixtures of similar hydrocarbons can be used to make paraffin, and thesemixtures can be solid, semi-solid, and/or oily. In some embodiments, theparaffin is a wax.

A wide range of different conventional impregnating processes can beused to at least partially embed material in the tissue sample. Thetissue samples can be mixed or combined with material that can permeatethe tissue sample so as to impart properties that facilitate a cuttingprocess. In this manner, the tissue samples are embedded. If the tissuesample is to be sectioned with a microtome or similar device, the tissuesample can be embedded in paraffin or other suitable material, such as aplastic resin. If the embedding material is paraffin, the paraffin canbe heated and melted. The hot liquid paraffin at least partiallyimpregnates the biological sample and is subsequently solidified.

At 270, the specimen is cut into mountable sections, placed on amicroscope slide, and then dried. A microtome can cut the specimen intothin sections, for example, slices on the order of about 5 microns toabout 6 microns thick. Each section can include a portion of the tissuesample and some of the embedding material.

Different techniques can be used to transfer the tissue specimens ontothe microscope slide at 280. In some embodiments, the cut sections arefloated on water to spread or flatten the sections. If the sections arepieces of paraffin embedded tissue, the sections can be floated on awarm bath to keep the sections in generally flat configurations, therebyreducing or preventing folding, creasing, or bending. A microscope slideis inserted into the warm bath. A front surface of the slide is used topick up the tissue specimens. To examine multiple tissue samples (e.g.,a set of tissue samples, each taken at a different location of asubject) using a single slide, a plurality of the tissue samples may besequentially floated onto the slide. These wet slides are then driedusing the slide dryer 100.

FIG. 6 shows a specimen 286 positioned on a droplet of transfer fluid282. The droplet of transfer fluid 282 can be water or other suitablefluid (including aqueous mediums) that may or may not contain anyadditives (e.g., wetting agents, reagents, dyes, etc.). If water isemployed, the water may be de-ionized water, double-distilled de-ionizedwater, purified water, or the like. The droplet of transfer fluid 282can be formed as the slide 130 is pulled out of the bath as describedabove. Alternatively, the droplet 282 can be deposited by directlydropping the transfer fluid onto the front surface 284 and thereafterplacing the specimen on top of the droplet. A droplet placed directlyonto surface 284 then functions to allow positioning of the specimen onthe front surface 284. The contact angle between the transfer fluid 282and the slide 130 is relatively small so that the specimen 286 is keptat the same general location, even if the slide 130 is moved between,for example, workstations or different equipment.

The surface tension of the transfer fluid 282 helps maintain a generallyflat configuration of the specimen 286 to limit, reduce, orsubstantially prevent unwanted irregularities of the specimen 286, suchas folding, creasing, protruding, buckling, or the like. Because thefluid 282 is trapped between the specimen 286 and the microscope slide130, the specimen 286 is kept away from the front surface 284.

The microscope slide 130 is held in a substantially vertical orientationto promote draining of the fluid 282 to reduce drying times. Theillustrated slide 130 is at an angle of inclination α defined by agenerally horizontal imaginary plane 291 (e.g., an imaginary planegenerally parallel to the support surface 140 of FIGS. 2 and 3) and theengagement face 160. Because the slide 130 lays flat against theconductive slide heater 110, the slide 130 is held at the same generalangle of inclination. The illustrated conductive slide heater 110extends generally along an imaginary plane 283 that defines an angle βwith the imaginary horizontal plane 291 that is greater than about 70degrees, 80 degrees, 85 degrees, or 90 degrees. A longitudinal axis 295of the slide 130 is generally parallel to the imaginary plane 283. Theangle β can be equal to or greater than about 80 degrees to keep themicroscope slide 130 at an angle of inclination α of about 80 degrees.Other angles are also possible, if needed or desired.

The engagement surface 160 is maintained at or above a melt point of theembedding material of the specimen 286 in order to conductively heat thespecimen 286. If the embedding material is paraffin with a melt pointbetween about 50 degrees Celsius and 57 degrees Celsius, the surface 160is kept at or above a temperature of about 50 degrees Celsius. Arrows277 represent heat being transferred from the heater 110 to the specimen286. When the embedding material melts, the melted material may floatalong the upper surface of the transfer fluid 282 and become depositedon the front surface 284. If the embedding material is more hydrophobicthan the microscope slide 130, the contact angle at which the transferfluid 282 interfaces with the surface 284 may increase, thereby causingthe fluid 282 to form an unstable droplet susceptible to migration alongthe surface 284. The tilted slide 130 promotes accumulation of thetransfer fluid 282 proximate a lower portion 287 of the specimen 286.The fluid 282 collects at a gap 285 between the specimen 286 and themicroscope slide 130 such that the fluid 282 eventually drains down thefront surface 284.

FIG. 6 also shows a position 296 (shown in phantom line) of the fluid282 after the contact angle has increased assuming the microscope 130was in a horizontal orientation instead of the vertical orientation.Because the illustrated microscope slide 130 is at an uprightorientation, the fluid 282 tends to accumulate at the gap 285 due togravity, as shown in FIG. 7. An upper portion 293 of the specimen 286can physically contact the heated surface 284 to limit, minimize, orsubstantially prevent migration of the specimen 286. The upper portion293, for example, may stick to the surface 284.

After a sufficient amount of fluid 282 has accumulated, it has atendency to drain downwardly away from the specimen 286, as indicated bythe arrow 297. The fluid 282 flows downwardly away from the specimen 286and travels down the surface 284. In this manner, at least a portion orsubstantially all of the fluid 282 trapped between the specimen 286 andthe surface 284 is removed. The specimen 286 thus overlies and is indirect physical contact with the surface 284. The fluid 282 caneventually run down the entire surface 284 to the bottom end of theslide 130.

The illustrated angle of inclination of FIG. 7 is greater than about 70degrees such that the beaded transfer fluid 282 drains after asufficient amount of the embedding material is melted so as toappreciably increase the contact angle between the fluid 282 and thesurface 284. In some embodiments, the angle of inclination is greaterthan about 75 degrees. Such embodiments are especially well suited tocause draining of residual transfer fluid (e.g., water) away fromrelatively small specimens, such as specimens containing tissue samplesobtained using core needle biopsies. Residual transfer fluid can bedrawn away at different speeds from different types and sizes ofspecimens, including relatively large specimens or small specimens. Insome embodiments, the angle of inclination is greater than about 75degrees to promote the rapid accumulation of transfer fluid 282 as thespecimen 286 is heated. Once the embedding material is heated to itsmelt point, the transfer fluid 282 rapidly beads up and is drainedtherefrom.

FIG. 8 shows the specimen-carrying slide 130 after completion of adrying period. The engagement face 160 can be maintained at atemperature equal to or greater than about 50 degrees Celsius and theambient air can be less than 30 degrees Celsius (e.g., a temperature ofabout 21 degrees Celsius). The slide 130 is placed against the heater110. The engagement face 160 heats the slide 130 such that the specimen286 is adhered to the surface 284 in a relatively short period of time,for example, less than or equal to about 5 minutes, 1 minute, 45seconds, 30 seconds, 20 seconds, or ranges encompassing such periods oftime. Most of the transfer fluid 282 is drained away from the specimen286 to avoid drying times associated with evaporating the entiredroplet. The length of the drying period can depend on the amount oftransfer fluid, the characteristics of the tissue of the specimen 286,characteristics of the embedding material, or the like.

The engagement face 160 of FIG. 7 can be maintained at or above atemperature of about 50 degrees Celsius, 55 degrees Celsius, or 65degrees Celsius, as well as within ranges encompassing such temperatures(e.g., a range of about 50 degrees Celsius to about 65 degrees Celsius).Such temperatures are especially well suited to melt paraffin or othermaterials with a relatively low melt point. In some embodiments, thespecimen 286 is adhered to the surface 284 in less than about 1 minute.For example, the specimen 286 can be adhered in about 10 seconds toabout 1 minute. In some embodiments, the engagement face 160 ismaintained at a temperature of about 65 degrees Celsius or above. Incertain embodiments, the engagement face 160 can be at a temperaturethat is less than, greater than, or equal to about 65 degrees Celsius,70 degrees Celsius, 80 degrees Celsius, or ranges of such temperatures.An infrared thermometer is used to measure the temperature of theengagement face 160 to maintain accuracy. The temperature of theengagement face 160 can be increased or decreased using feedback fromthe thermometer to decrease or increase drying times.

The engagement face 160 can be maintained at a somewhat constanttemperature during the heating period for consistent drying. The slideheater 110 is thus capable of drying slides without appreciabletemperature changes. By way of example, the engagement face 160 can bemaintained at a generally constant temperature at or above a melt pointof embedding material to ensure short drying times. In some embodiments,the temperature of the engagement face 160 is kept within an operatingtemperature range that is above the melt point. The operatingtemperature range can be 50 degrees Celsius to 60 degrees Celsius, 55degrees Celsius to 65 degrees Celsius, or 60 degrees Celsius to 70degrees Celsius. Other ranges are also possible.

The engagement face 160 can be pre-heated to immediately transfer heatto the slide 130 upon contact. Pre-heating can be used to avoid ramp-uptimes associated with cyclic heating processes. Slides can be repeatedlyloaded onto the slide dryer 100 without waiting for the engagement face160 to reach a certain temperature. Of course, the temperature of theengagement face 160 may decrease slightly as the slide 130 absorbs heat.These effects can be minimized or avoided by continuously generatingheat with the slide heater 110.

In other embodiments, the engagement face 160 can be heated after theslide 130 placed against the face 160. To reduce energy consumption, theengagement face 160 can be maintained at a low temperature, for example,at about room temperature or at a temperature between room temperatureand a desired temperature for drying. In some embodiments, the lowtemperature is a standby temperature. For example, the engagement face160 can be kept at a standby temperature in a range of about 25 degreesCelsius to about 50 degrees Celsius. The temperature of the engagementface 160 is increased to at least about 50 degrees Celsius during orafter loading of the slides 130. After drying, the engagement surface160 returns to the standby temperature. A wide range of different typesof heating cycles can be employed to reduce or limit the amount ofenergy used to during drying processes.

After drying, the slide 130 is removed from the slide dryer 100. Toincrease the rate of cooling of the specimen 286 and therefore decreaseprocessing time, the conductive slide heater 110 can also includecooling elements (e.g., Peltier elements) used to rapidly absorb heatfrom the dried specimen-bearing slide 130. Once the specimen-bearingslide 130 is sufficiently cooled, it can be removed from the slide dryer100.

At step 289, the specimen 286 is stained for examination. The specimencan also be baked, de-waxed, de-paraffinized, or the like. In someembodiments, a stain is applied to the specimen 286 after performing ade-paraffinizing process. The microscope slide is then cover slipped forsubsequent optical examination.

At step 290, the specimen 286 can be examined using optical equipment(e.g., a microscope), optical instruments, or the like. Different typesof examination processes can be used to perform a wide range ofdifferent tissue analyses used to obtain information about pathology,tissue composition, and the tissue architecture. This information can beused by a physician to diagnose different types of illnesses and toperform various medical research.

Referring to FIG. 9, a slide dryer 300 includes a conductive slideheater 310, a base 312, and a cover 314. The base 312 includes acontroller 320 for controlling operation of the conductive slide heater310. The cover 314 can enclose and surround the conductive slide heater310 to prevent unwanted contaminates from landing on thespecimen-carrying microscope slides. The base 312 includes a collector337 surrounding the slide conductive heater 310. The collector 337 cancollect residual transfer fluid or other materials that are removed fromthe slides.

The illustrated conductive slide heater 310 includes a plurality of heatgenerating support elements 330 a-h (collectively 330) spaced apart fromone another. The support elements 330 can be independently operated oroperated together and are oriented at the same or different inclines.The illustrated elements 330 are generally parallel to one another andspaced to allow at least one generally vertically oriented microscopeslide to be inserted between a pair of adjacent elements 330. Each ofthe support elements 330 can include one or more energizable thermaldevices (e.g., electro-thermal elements). In other embodiments, a backplate 441 extending between the support elements 330 has thermal devices(e.g., internal thermal devices) capable of generating heat that isconducted through the support elements 330.

In operation, microscope slides can lean against respective supportelements 330. The cover 314 can be moved over the slide heater 310 asindicated by the arrows 339. The conductive slide heater 310 can dry anentire row of vertically oriented specimen-bearing microscope slides.After the microscope slides are processed, the cover 314 is removed toaccess and remove the microscope slides.

FIG. 10 shows a heater assembly 360 that includes a frame 361 and aplurality of conductive slide heaters 362, 364 coupled to the frame 361.The conductive slide heaters 362, 364 can be generally similar to theslide conductive heater 310 of FIG. 9. The heater assembly 360 can beincorporated into different types of slide processing systems, such asan automated slide processing system or stand-alone slide dryers, andmay include a controller, power sources, or the like.

FIG. 11 shows an apparatus 400 that includes a drying station 402 and aplurality of processing stations 404, 406, 408. A controller 410controls operation of the drying station 402 and one or more of theprocessing stations 404, 406, 408. The illustrated controller 410 iscommunicatively coupled to and commands each of the stations 402, 404,406, 408. Microscope slides can be automatically processed (e.g., via aprocess that is substantially free of human intervention) using theapparatus 400. For example, the controller 410 can control the amount ofheat produced by a slide dryer 401 at the station 402 (FIG. 13), rate ofdrying, length of time of the drying period, or other processingparameters, preferably while keeping thermal damage to the tissue sampleat or below a desired level.

As used herein, the term “processing station” includes, withoutlimitation, a baking station, a material removal station (e.g., ade-waxing station, a de-paraffinizing station, or the like), stainingstation, cover-slipping station, or the like. For example, theprocessing stations 404, 406, 408 can be a de-paraffinizing station,staining station, and cover-slipping station, respectively.

A transport device 418 transports specimen-bearing microscope slidesbetween the drying station 402 and the other stations 404, 406, 408. Thetransport device 418 can include, without limitation, one or moreelevators, slide handlers, slide trays, slide holders, or the like.Slide handlers can include, but are not limited to, slide manipulators,X-Y-Z transport systems, robotic systems, or other automated systemscapable of receiving and transporting slides. A robotic system caninclude, without limitation, one or more pick and place robots, roboticarms, or the like.

Referring to FIGS. 11-13, the drying station 402 includes the slidedryer 401 and a slide handler 420, illustrated as a robotic slidehandler. The slide dryer 401 generates heat for conductively heating thespecimen-carrying microscope slides. The robotic slide handler 420includes an arm 421 and an end effector 423 capable of picking up andcarrying slides between the conductive slide heater 401 and a slidetransporter 424, illustrated schematically in FIG. 13. The slide dryer401 can be generally similar to the slide dryer 100 of FIGS. 1-3 or theslide dryer 300 of FIG. 10. Various types of other automated slideprocessing systems can also have the slide dryers and other featuresdisclosed herein. For example, U.S. application Ser. No. 10/414,804(U.S. Publication No. 2004/0002163) discloses various types of slidetransporters, processing stations, and the like that can be used with orincorporated into the embodiments and features disclosed herein.

Wet microscope slides carrying freshly cut tissue specimens can beprocessed using the apparatus 400. An access door 430 can be opened, anda user can load specimen-bearing slides into the transport device 418.The transport device 418 can load the slides into the dryer station 402.After drying the specimen-bearing slides, the slides are sequentiallydelivered to the stations 404, 406, 408. The transport device 418 ofFIG. 13 includes an elevator system 430 and a movable platform 434,shown carrying the slide transporter 424. The elevator system 430 movesthe transporter 424 up and down a rail 440.

In some methods of using the apparatus 400, specimen-carrying microscopeslides are loaded onto a slide tray, which is placed on the platform434. The slide handler 420 loads the specimen-carrying microscope slidesinto the slide dryer 401. The slide dryer 401 dries thespecimen-carrying microscope slides. After the specimen-carryingmicroscope slides are dried a sufficient amount, the slide handler 420transports the slides back to the transporter 424.

The transporter 242 is vertically lowered and positioned adjacent to theprocessing station 404 for de-paraffinizing. The station 404 is capableof removing at least a portion of the embedding material of thespecimen. The de-paraffinizing station 404 can be a bath-type,de-paraffinizing station or a spray-type, de-paraffinizing station. Theillustrated de-paraffinizing station 404 includes a modular compartment414 and includes one or more wash dispense nozzles 416 directeddownwardly. De-paraffinizing substances are delivered onto the specimensusing the nozzles 416. After removing the embedding material (e.g.,paraffin), the slides can be rinsed with substances, such as de-ionizedwater, to remove the de-paraffinizing substance and the extra paraffinleaving the bare tissue sample adhered to the microscope slide.

Various de-paraffinizing substances may be used at the station 404. Forexample, the de-paraffinizing substances can be fluids, for example,aqueous-based fluids that promote separation of paraffin and tissuespecimens, such as those disclosed in U.S. Pat. No. 6,855,559, issuedFeb. 15, 2005 and U.S. Pat. No. 6,544,798, issued Apr. 8, 2003,including de-ionized water, citrate buffer (pH 6.0-8.0), tris-HCl buffer(pH 6-10), phosphate buffer (pH 6.0-8.0), acidic buffers or solutions(pH 1-6.9), basic buffers or solutions (pH 7.1-14), or the like. Thesubstance may also contain one or more ionic or non-ionic surfactants.The de-paraffinizing substances can be heated. For example, thesubstances (e.g., fluids) may be heated to a temperature greater thanthe melting point of the embedding material, e.g., between 60-70 degreesCelsius. U.S. Pat. No. 7,303,725, issued Dec. 4, 2007, discloses variouscomponents (e.g., probes, filters, sprayers, etc.) for use withde-paraffinizing substances.

In some embodiments, the station 404 also includes one or more heatingelements for baking the embedding material. The slides can be heated tosoften the embedding material to facilitate material removal.

After the station 404 has processed the specimen-carrying slides, thetransport system 424 delivers the specimen-carrying slides to thestation 406 for staining. A desired stain is applied to the tissuesamples. The stain can be a biological or chemical substance which, whenapplied to targeted molecules in tissue, renders the tissue detectableunder an instrument. Stains include, without limitation, detectablenucleic acid probes, antibodies, hematoxylin, eosin, and dyes (e.g.,iodine, methylene blue, Wright's stain, etc.).

After the specimens are stained, the specimen-bearing slides aretransported to the cover-slipping station 408. In other embodiments, thestation 408 is a drying station. The station 408 dries the stainedslides and the slides are ready for cover slipping. In some embodiments,the drying station 408 conductively heats the stained specimens using aslide dryer, such as those discussed in connection with FIGS. 1-10. Inother embodiments, the drying station 408 is in the form of a convectionoven or microwave oven.

The apparatus 400 can also include other types of processing stations.The number, configurations, and types of processing stations can beselected based on the types of processing to be performed. For example,U.S. Pat. No. 7,396,508 discloses apparatuses for staining and treatingtissues. U.S. Pat. No. 7,396,508 is incorporated herein by reference inits entirety. In some embodiments, the processing station 406 includes acarousel type system, such as the carousel system disclosed in U.S. Pat.No. 7,396,508.

The various embodiments described above can be combined to providefurther embodiments. All of the U.S. patents, U.S. patent applicationpublications, U.S. patent applications, foreign patents, foreign patentapplications and non-patent publications referred to in thisspecification and/or listed in the Application Data Sheet areincorporated herein by reference, in their entirety. Aspects of theembodiments can be modified, if necessary to employ concepts of thevarious patents, applications and publications to provide yet furtherembodiments.

These and other changes can be made to the embodiments in light of theabove-detailed description. In general, in the following claims, theterms used should not be construed to limit the claims to the specificembodiments disclosed in the specification and the claims, but should beconstrued to include all possible embodiments along with the full scopeof equivalents to which such claims are entitled. Accordingly, theclaims are not limited by the disclosure.

I claim:
 1. A method for processing specimen-bearing microscope slidesusing an automated slide processing apparatus having a first station, asecond station, and a conductive heater, the method comprising:receiving, via an access door of the automated slide processingapparatus, a slide tray fixedly holding a plurality of microscope slidesin a spaced apart arrangement; robotically delivering the plurality ofmicroscope slides to the first station configured to hold the pluralityof microscope slides at an angle of inclination greater than 75 degreeand to receive liquid drained from the plurality of microscope slides;conductively heating the plurality of microscope slides using theconductive slide heater; and after conductively heating the plurality ofmicroscope slides, robotically transporting the plurality of microscopeslides to a second station, individually dispensing reagents onto uppersurfaces of the plurality of microscope slides at the second station,and robotically transporting the plurality of microscope slides awayfrom the second station.
 2. The method of claim 1, further comprisingrobotically placing the plurality of microscope slides on the conductiveslide heater.
 3. The method of claim 1, further comprising roboticallyrotating the microscope slides carrying specimens to a verticalorientation for delivery to the first station.
 4. The method of claim 1,further comprising robotically applying a series of reagents onto theplurality of microscope slides while the plurality of microscope slidesare held by the slide tray.
 5. The method of claim 1, whereinindividually dispensing the reagents onto the upper surfaces includesoutputting reagents from one or more nozzles positioned above the uppersurfaces.
 6. The method of claim 1, further comprising roboticallytransporting the plurality of microscope slides between the first andsecond stations using a transport device.
 7. A method for processingspecimen-bearing microscope slides using an automated slide processingapparatus, the method comprising: receiving, via an access port, a slidetray fixedly holding a plurality of microscope slides; roboticallydelivering the plurality of microscope slides to a first station,wherein the plurality of microscope slides at a substantially verticalorientation and held apart from one another; and after draining liquidfrom the plurality of microscope slides oriented at an angle ofinclination greater than 75 degrees, robotically delivering the slidetray carrying the plurality of microscope slides to a second station,individually dispensing reagents onto upper surfaces of the plurality ofmicroscope slides located at the second station to stain specimenscarried by the plurality of microscope slides, and roboticallytransporting the slide tray carrying the plurality of microscope slideswith the stained specimens away from the second station.
 8. The methodof claim 7, further comprising robotically placing the plurality ofmicroscope slides on a conductive slide heater.
 9. The method of claim7, further comprising robotically moving the plurality of microscopeslides to a vertical orientation for delivery of the plurality ofmicroscope slides to the first station.
 10. The method of claim 7,further comprising robotically transporting the plurality of microscopeslides to a series of stations to sequentially process the microscopeslides.
 11. The method of claim 7, wherein individually dispensing thereagents onto the upper surfaces includes outputting the reagents fromone or more nozzles positioned above the upper surfaces.
 12. The methodof claim 7, further comprising robotically transporting the plurality ofmicroscope slides between the first and second stations using atransport device.
 13. The method of claim 7, further comprising dryingthe plurality of microscope slides oriented at the substantiallyvertical orientation.
 14. An automated slide processing apparatus,comprising: an access port configured to receive a slide tray fixedlyholding a plurality of microscope slides; a first station; a secondstation; and a controller programmed to cause the automated slideprocessing apparatus to perform actions including robotically deliveringthe plurality of microscope slides to the first station configured tohold the plurality of microscope slides at a substantially verticalorientation; and after draining liquid from the plurality of microscopeslides oriented at the substantially vertical orientation, roboticallydelivering the slide tray carrying the plurality of microscope slides tothe second station, individually dispensing reagents onto upper surfacesof the plurality of microscope slides located at the second station tostain specimens carried by the plurality of microscope slides, androbotically transporting the slide tray carrying the stained specimensand plurality of microscope slides away from the second station.
 15. Theautomated slide processing apparatus of claim 14, wherein the actionsfurther include robotically placing the plurality of microscope slideson a conductive slide heater.
 16. The automated slide processingapparatus of claim 14, wherein the actions further include roboticallymoving the plurality of microscope slides carrying wet specimens to thesubstantially vertical orientation for delivery of the plurality ofmicroscope slides to the first station.